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Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application.

ABSTRACT: Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes in development pipelines. Innovative antibacterial therapeutics and strategies are, therefore, in grave need. For the last twenty years, antimicrobial enzymes encoded by bacteriophages, viruses that can lyse and kill bacteria, have gained tremendous interest. There are two classes of these phage-derived enzymes, referred to also as enzybiotics: peptidoglycan hydrolases (lysins), which degrade the bacterial peptidoglycan layer, and polysaccharide depolymerases, which target extracellular or surface polysaccharides, i.e., bacterial capsules, slime layers, biofilm matrix, or lipopolysaccharides. Their features include distinctive modes of action, high efficiency, pathogen specificity, diversity in structure and activity, low possibility of bacterial resistance development, and no observed cross-resistance with currently used antibiotics. Additionally, and unlike antibiotics, enzybiotics can target metabolically inactive persister cells. These phage-derived enzymes have been tested in various animal models to combat both Gram-positive and Gram-negative bacteria, and in recent years peptidoglycan hydrolases have entered clinical trials. Here, we review the testing and clinical use of these enzymes.

SUBMITTER: Danis-Wlodarczyk KM

PROVIDER: S-EPMC8698926 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application.

Danis-Wlodarczyk Katarzyna M KM Wozniak Daniel J DJ Abedon Stephen T ST

Antibiotics (Basel, Switzerland) 20211206 12

Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes in development pipelines. Innovative antibacterial therapeutics and strategies are, therefore, in grave need. For the last twenty years, antimicrobial enzymes encoded by bacteriophages, viruses that can lyse and kill bacteria, have gained tremendou ...[more]

PMID: 34943709

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Project description:BackgroundIn nosocomial settings, vancomycin-resistant Enterococcus faecalis is a major health threat leading to increased morbidities, mortalities, and treatment costs. Nowadays, several approaches are under investigation to enhance the activity of or replace the traditional antibiotics. Bacteriophage therapy was sought as a potential approach for combating E. faecalis infections. The present study focuses on isolating and characterizing bacteriophage against clinical multi-drug resistant (MDR) E. faecalis strain Lb-1492. The phage stability, lytic activity, host-range, latent period, burst size, the ability to detach the pre-formed biofilm and destroy entrapped cells were investigated. The phage genome was purified, sequenced, and subjected to bioinformatics analysis for identifying and characterizing its features, as well as, the suitability for clinical application. Finally, the ability of the phage to rescue mice from deadly, experimentally induced E. faecalis bacteremia was evaluated.ResultsA virulent phage was isolated from sewage water against a clinical MDR E. faecalis isolate. Morphological and genomic studies indicated that the phage belongs to the Efquatrovirus genus, with a long tail, icosahedral head and a linear double-stranded DNA genome of approximately 42.9 kbp. The phage was named vB_Efa_ZAT1 (shortly ZAT1). It demonstrated a shorter latent period and larger burst size than regular-tailed phages, and a characteristic stability over a wide range of pH and temperatures, with the optimum activity at pH 7.4 and 37 °C, respectively. Phage ZAT1 showed a narrow spectrum of activity and a characteristic biofilm disruption ability. The phage managed successfully to control E. faecalis-induced bacteremia in mice models, which was lethal within 48 h in the control group. An intraperitoneal injection of 3 × 108 PFU of the phage solution given 1 h after the bacterial challenge was sufficient to save all the animals, completely reversing the trend of 100% mortality caused by this bacterium.ConclusionsPhage therapy can be a promising alternative to traditional antibiotics in the post-antibiotic era with a significant antimicrobial and antibiofilm activities against MDR E. faecalis.

Dataset Information

Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application.

Publications

Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application.

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